A Mad2-Mediated Translational Regulatory Mechanism Promoting S-Phase Cyclin Synthesis Controls Origin Firing and Survival to Replication Stress.

ABSTRACT: Cell survival to replication stress depends on the activation of the Mec1^ATR-Rad53 checkpoint response that protects the integrity of stalled forks and controls the origin firing program. Here we found that Mad2, a member of the spindle assembly checkpoint (SAC), contributes to efficient origin firing and to cell survival in response to replication stress. We show that Rad53 and Mad2 promote S-phase cyclin expression through different mechanisms: while Rad53 influences Clb5,6 degradation, Mad2 promotes their protein synthesis. We found that Mad2 co-sediments with polysomes and modulates the association of the translation inhibitor Caf20^4E-BP with the translation machinery and the initiation factor eIF4E. This Mad2-dependent translational regulatory process does not de

SUBMITTER: Gay S 

PROVIDER: S-EPMC5972228 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature